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C Ward

Publications and source records attributed to C Ward.

At least 91 records · Page 5Linked to original sources
PubMed1997

Immunopathological changes in the airways of stable lung transplant recipients.

BACKGROUND: Pathological obliterative bronchiolitis, characterised by inflammation and occlusion of airways, is a serious complication of lung transplantation. Endobronchial biopsy (EBB) provides a means of examining transplanted airways. This study aimed to investigate the role of EBB samples in revealing early signals of airway injury. METHODS: In 18 stable lung transplant recipients with close to maximal lung function (median FEV1, best after transplantation 100%, interquartile range 98-100%) EBB samples were taken simultaneously with transbronchial biopsy samples and bronchoalveolar lavage (BAL) fluid (median 195 days after transplantation). OCT embedded specimens were snap frozen on an isopentane slurry made with liquid nitrogen and 7 microns sections were stained with monoclonal antibodies using a three stage immunoperoxidase method. RESULTS: Compared with nine non-transplanted control subjects, EBB specimens from the stable transplant group had significantly increased CD8 positivity (median 53 versus 27 cells/mm basement membrane, p = 0.04; 95% CI for the difference 1 to 46)) and increased HLA-DR positivity (median 84 versus 26 cells/mm basement membrane, 95% CI for the difference 6 to 115). There was an increase in CD68 positive cells in the EBB specimens from transplant recipients of borderline significance (median 92 versus 68, p = 0.08, 95% CI for the difference 1 to 84). CD3, CD4, and CD25 counts were similar in the two groups. EBB findings were not influenced by age, sex, indication for transplant, immunosuppression doses or levels, nor the presence of airway commensals in the BAL fluid. CONCLUSIONS: EBB is practicable in a transplant setting and provides information about bronchial inflammatory changes. It is likely that there is ongoing inflammation, possibly rejection mediated, even in healthy lung transplant recipients despite triple immunosuppression.

Adult↗
PubMed1997

Bronchial hyperresponsiveness in lung transplant recipients: lack of correlation with airway inflammation.

BACKGROUND: Bronchial hyperresponsiveness (BHR) to methacholine has been reported to occur in most lung transplant recipients. BHR to physical stimuli such as exercise and non-isotonic aerosols has not been as extensively studied in this subject population. This report aims to assess the presence and degree of BHR to methacholine and hypertonic saline in stable lung transplant recipients and to relate it to the presence of airway inflammation. METHODS: Ten patients undergoing bilateral sequential lung transplantation and six heart-lung transplant recipients, all with stable lung function, were recruited 66-1167 days following transplantation. Subjects underwent a methacholine challenge and bronchoscopy for sampling of bronchoalveolar lavage fluid, transbronchial and endobronchial biopsy tissues. Hypertonic saline challenge was performed six days later. RESULTS: Nine of the 16 transplant recipients had positive methacholine challenges (geometric mean PD20 0.18 mg, interquartile range 0.058-0.509) and three of these subjects also had positive hypertonic saline challenges (PD15 = 2.3, 33.0, and 51.5 ml). No clear relationship was found between BHR to either methacholine or hypertonic saline and levels of mast cells, eosinophils or lymphocytes in samples of biopsy tissue or lavage fluid. CONCLUSIONS: Most of the lung transplant recipients studied were responsive to methacholine and unresponsive to hypertonic saline. BHR was not clearly related to airway inflammation, suggesting an alternative mechanism for BHR following lung transplantation from that usually assumed in asthma.

Adult↗
PubMed1997

Scar collagen deposition in the airways of allografts of lung transplant recipients.

Collagen subtype deposition has not been studied in the airways of transplanted lungs. As part of rejection, a series of immunologic insults results in a remodeling of the allograft. In chronic rejection, changes in the airway leading to obliterative bronchiolitis syndrome (OBS) are particularly important. To better understand the mechanism of OBS occurring in chronic lung rejection, we investigated deposition of three fibrillar collagens (type I, III, V) in airway biopsies of lung allografts taken from 10 clinically well lung transplant recipients (wLTR) and eight lung transplant recipients (LTR) with OBS (OBLTR) using an immunoperoxidase method. Collagen III deposition and the ratio of collagen type III to type I were found to be significantly increased in OBLTR compared with wLTR (p < 0.05), and the latter correlated inversely with both FEF(25-75) (r = -0.69; p < 0.05) and FEV1 (r = 0.62; p = 0.05) in OBLTR. This suggests that an increased proportion of collagen III in the airway walls of transplanted lungs might be an early signal of the progression to terminal chronic lung allograft dysfunction. The changes in the ratio of type III to type I collagen in the airways of lung allografts may provide important insights into the process of airway remodeling in chronic lung rejection.

Adult↗
PubMed1997

Albumin is not suitable as a marker of bronchoalveolar lavage dilution in interstitial lung disease.

We have investigated the origin of raised bronchoalveolar lavage (BAL) albumin levels in interstitial lung diseases (ILDs), and the hypothesis that acute flux during BAL might contribute to the elevated levels of albumin in samples from ILD patients. Total albumin concentrations were measured in three separately aspirated 60 mL aliquots of BAL in 12 ILD patients and seven control subjects, and previous work indicating that BAL albumin levels may be raised in ILD was confirmed. In addition, the extent of acute flux from the circulation was investigated using 1.48 MBq of 125I-radiolabelled human serum albumin injected intravenously shortly before the procedure. It was found that acute albumin flux occurred in only a minority of the ILD patients (4 out of 12) and control subjects (3 out of 7). These results indicate that the elevated levels of plasma proteins, such as albumin, documented in BAL aspirates from ILD patients are not an artefact of the BAL procedure related to increased vascular permeability, and that this finding is more likely to be related to the effects of chronic inflammatory changes in the lung due to the underlying disease. The work confirms that albumin is unsuitable as a denominator for the normalization of bronchoalveolar lavage solute results, since levels can vary, both as a result of acute flux and, more frequently, because of disease activity.

Adult↗
PubMed1997

Airway versus transbronchial biopsy and BAL in lung transplant recipients: different but complementary.

Lung transplantation is now an established therapeutic intervention for end-stage cardiopulmonary disease in humans. Chronic rejection, in the form of bronchiolitis obliterans syndrome (BOS), remains the commonest cause of morbidity and mortality in those surviving more than 3 months. The pathology of BOS involves airway changes. We have evaluated the potential for endobronchial biopsies (EBB) to complement existing sampling methods used in allograft monitoring and have compared the results of EBB findings with those of bronchoalveolar lavage (BAL) and transbronchial biopsy (TBB) in 18 clinically stable patients. We found that all the EBB had inflammatory cells present but that only five TBB specimens had evidence of inflammation, with airway material being present in 78% of the TBB. Paired BAL and EBB yielded different results, with no correlations between total macrophages, lymphocytes, CD4+ cells or CD8+ cells. We conclude that endobronchial biopsies are potentially useful as an additional sample for the monitoring of inflammation in lung allografts, since they yield different, and potentially complimentary, information to bronchoalveolar lavage and transbronchial biopsy.

Adult↗
PubMed1997

IL-5 production by bronchoalveolar lavage and peripheral blood mononuclear cells in asthma and atopy.

There is increasing evidence to suggest a key role for interleukin-5 (IL-5) in the regulation of airway eosinophilia in asthma. We compared the capacity for IL-5 production in atopic asthmatic, nonatopic asthmatic, atopic nonasthmatic and normal subjects, and evaluated the usefulness of peripheral blood cells for reflecting airway cell reactivity. Bronchoalveolar lavage (BAL) cells and peripheral blood mononuclear cells (PBMC) from 12 atopic and 10 nonatopic asthmatics (without inhaled steroid therapy), 9 atopic nonasthmatics, and 10 normal controls were cultured with or without house dust mite (HDM, 10 microg x mL-1) stimulation. CD4+ T-cell activation, IL-5 and interferon-gamma (IFN-gamma) production in the cultures were assessed. Both for BAL and PBMC samples, atopic and nonatopic asthmatic subjects showed comparable spontaneous production of IL-5, which was significantly higher than that either for atopic nonasthmatics or normal controls (p<0.05 or p<0.01). There was a significant correlation between the percentage of eosinophils in BAL and spontaneous production of IL-5 by BAL cells in both asthmatic groups (p<0.05 or p<0.01). Both these parameters were also associated with asthmatic airway narrowing as denoted by a negative relationship with baseline forced expiratory volume in one second (FEV1) as percentage predicted (p<0.05 and p<0.01, respectively). In contrast, IFN-gamma production by unstimulated BAL cells from normal controls was higher than that for BAL cell cultures of nonatopic asthmatic subjects (p<0.05). Following HDM stimulation, both atopic groups had comparable positive responses in terms of CD4+ T-cell activation, but there was relatively greater IL-5 production in asthmatic PBMC (p<0.05) and, in particular, BAL cell cultures (p<0.01). These findings suggest that elevated IL-5 production is a common feature of BAL cells and PBMC in atopic and nonatopic asthma. In addition, atopic asthmatics show greater IL-5 production in response to specific allergen compared with atopic nonasthmatics, an effect most marked in BAL cells compared to PBMC. Hence, peripheral blood mononuclear cells can reflect cytokine immunoreactivity of airway cells, but lack local cellular interactions, which limits their usage in asthma research.

Adult↗
PubMed1996

Bidding to build.

Explore the source record for details and available documents.

Economics, Hospital↗
PubMed1996

Spinal cord infarct after arterial switch associated with an umbilical artery catheter.

Paraplegia after an open heart operation in a neonate is a rare complication. We report a case of a infant in whom paraplegia developed after a successful arterial switch operation for transposition of the great arteries. The infant was monitored and resuscitated in the preoperative period with umbilical arterial and venous catheter tips located in the midthoracic region. He likely suffered a clinically silent thromboembolic event predisposing him to a localized hemorrhagic infarction during the repair.

Cardiopulmonary Bypass↗
PubMed1996

Reproducibility of orthostatic hypotension in symptomatic elderly.

PURPOSE: Variations in the reported prevalence of orthostatic hypotension (4% to 33%) are attributed to population selection and varied criteria used to define orthostatic hypotension. Variation in the reproducibility of hemodynamic responses to orthostasis could be a further confounding variable. The purpose of this study was to evaluate reproducibility of orthostatic blood pressure changes in patients with documented symptomatic orthostatic hypotension. PATIENTS AND METHODS: Forty outpatients (mean age 77+/- 8 years; 24 women) were recruited after initial presentation to a morning outpatient clinic with postural symptoms of dizziness (92%), falls (67.5%), or syncope (30%). Patients had a symptomatic drop in orthostatic systolic blood pressure of >20 mm Hg documented in clinic. Subsequent cardiovascular assessment included autonomic function tests, carotid sinus massage (supine and erect), and prolonged head-up tilt tests. Blood pressure and heart rate measurements were repeated during standing and head-up tilt on two further attendances in the morning. RESULTS: A total of 67.5% patients had a drop in systolic blood pressure of >20 mm Hg on both visits during orthostatic stimuli; in the remainder, the response was not reproducible, and 5% had no significant orthostatic drop at either attendance. In 19 patients autonomic function tests were abnormal; orthostatic hypotension was reproducible in 79% of this group. In patients with normal autonomic function tests, 57% had reproducible orthostatic hypotension, of which only 60% were reproducible in those patients when further assessed in the afternoon. CONCLUSIONS: Orthostatic blood pressure responses may not be reproducible in patients with documented symptomatic orthostatic hypotension, particularly if autonomic function is normal and measurements are taken in the afternoon. Repeated systolic blood pressure measurements in the morning may be necessary to make a diagnosis in older patients with suspected orthostatic hypotension.

Accidental Falls↗
PubMed1996

Ischemic heart disease in patients with end-stage renal disease.

Prevention and treatment of cardiovascular disease and, in particular, ischemic heart disease (IHD) in an increasingly elderly and diabetic population of patients with end-stage renal disease (ESRD) pose a challenge to all members of the renal failure treatment program. The patient described herein presents such a challenge, illustrating risk factors for IHD, the dilemma of performing surgery given his age and comorbid conditions, and the impact of IHD on his quality of life and capacity to function independently. The coordinated efforts of the nephrologist, cardiologist, cardiac surgeon, rehabilitation specialist, nutritionist, primary nurse, and social worker all contributed to a successful intervention.

Aged↗
PubMed1996

Textured or smooth implants for submuscular breast augmentation: a controlled study.

Capsular contracture consistently has been the most frequently noted complication of submuscular and subglandular breast augmentation. The etiology of this complication is still unknown, although silicone bleed, hematoma, infection, foreign bodies, and surgical trauma have been implicated. In this prospective, double-blind study, 61 women undergoing submuscular breast augmentation were randomized between Dow Corning textured and smooth-walled silicone gel implants. Any consequent capsular contracture was assessed by an independent plastic surgeon and also by the patients themselves. Objective evaluation was made by applanation tonometry. It was found that depending on doctors, patients, and objective method used, 3 to 9 percent grade III and IV encapsulation followed submuscular augmentation with textured implants and 10 to 20 percent with smooth-walled implants after 1 year. The differences were significant according to both patient assessment and applanation tonometry but not according to the physicians' evaluations. There was no correlation of capsular contracture with the age of the patient, duration of the operation, or degree of blood loss. There was a small but inconclusive difference in capsular contracture rate that favored the placement of textured rather than smooth implants in the submuscular pocket.

Adult↗
PubMed1996

Bronchoalveolar lavage in asthma research.

A great deal of information about the pathophysiology of asthma and its treatment have been obtained through the use of bronchoalveolar lavage (BAL), especially in combination with airway biopsies. The introduction of highly sophisticated methods for examining BAL aspirate, including fluorocein activated cell scanning (FACS) analysis and molecular biology techniques has emphasized the potential power of this method of airway investigation. For those contemplating the use of BAL in asthma research programmes, we hope that this review will provide a useful insight into the current state of knowledge about the technique and its application, and that it will provide a solid platform for study design.

Asthma↗
PubMed1996

Intrasubject variability in airway inflammation in biopsies in mild to moderate stable asthma.

We have studied intrasubject variability with respect to counts of immunostained inflammatory cells in snap frozen endobronchial biopsies from a group of patients with clinically mild to moderate stable asthma. Fiberoptic bronchoscopy was used to obtain endobronchial biopsies from the upper and lower lobes in 12 volunteer subjects with asthma on two separate occasions 1 mo apart. During this period there was no significant change in asthma treatment, symptom scores, pulmonary function, or airway hyperresponsiveness. With the aid of immunohistochemistry and interactive image analysis, subepithelial counts for T lymphocytes, T-lymphocyte subsets, and eosinophils were made. There was wide intrasubject variability between anatomic site and with time for all the inflammatory cell counts. In each case the intrasubject variability with time was greater than lobar differences. Power calculations were made to establish the optimal sample size required for each marker. We conclude that even in stable asthma considerable biologic variability compounds sampling variability. Such sources of variability need to be borne in mind when calculating the likely power of intervention studies using biopsy data as end points. Power calculations suggest that approximately 15 subjects would be an optimal number with little advantage in increasing beyond this.

Adolescent↗